Jim L. Rupert

Inspiratory muscle training attenuates the human respiratory muscle metaboreflex.

We hypothesized that inspiratory muscle training (IMT) would attenuate the sympathetically mediated heart rate (HR) and mean arterial pressure (MAP) increases normally observed during fatiguing inspiratory muscle work. An experimental group (Exp, n= 8) performed IMT 6 days per week for 5 weeks at 50% of maximal inspiratory pressure (MIP), while a control group (Sham, n= 8) performed IMT at 10% MIP. Pre‐ and post‐training, subjects underwent a eucapnic resistive breathing task (RBT) (breathing frequency = 15 breaths min−1, duty cycle = 0.70) while HR and MAP were continuously monitored. Following IMT, MIP increased significantly (P < 0.05) in the Exp group (−125 ± 10 to −146 ± 12 cmH2O; mean ±s.e.m.) but not in the Sham group (−141 ± 11 to −148 ± 11 cmH2O). Prior to IMT, the RBT resulted in significant increases in HR (Sham: 59 ± 2 to 83 ± 4 beats min−1; Exp: 62 ± 3 to 83 ± 4 beats min−1) and MAP (Sham: 88 ± 2 to 106 ± 3 mmHg; Exp: 84 ± 1 to 99 ± 3 mmHg) in both groups relative to rest. Following IMT, the Sham group observed similar HR and MAP responses to the RBT while the Exp group failed to increase HR and MAP to the same extent as before (HR: 59 ± 3 to 74 ± 2 beats min−1; MAP: 84 ± 1 to 89 ± 2 mmHg). This attenuated cardiovascular response suggests a blunted sympatho‐excitation to resistive inspiratory work. We attribute our findings to a reduced activity of chemosensitive afferents within the inspiratory muscles and may provide a mechanism for some of the whole‐body exercise endurance improvements associated with IMT.

Evidence for a Genetic Basis for Altitude Illness: 2010 Update

Altitude illness refers to a group of environmentally mediated pathophysiologies. Many people will suffer acute mountain sickness shortly after rapidly ascending to a moderately hypoxic environment, and an unfortunate few will develop potentially fatal conditions such as high altitude pulmonary edema or high altitude cerebral edema. Some individuals seem to be predisposed to developing altitude illness, suggesting an innate contribution to susceptibility. The implication that there are altitude-sensitive and altitude-tolerant individuals has stimulated much research into the contribution of a genetic background to the efficacy of altitude acclimatization. Although the effect of altitude attained and rate of ascent on the etiology of altitude illness is well known, there are only tantalizing, but rapidly accumulating, clues to the genes that may be involved. In 2006, we reviewed what was then known about the genetics of altitude illness. This article updates that review and attempts to tabulate all the available genetic data pertaining to these conditions. To date, 58 genes have been investigated for a role in altitude illness. Of these, 17 have shown some association with the susceptibility to, or the severity of, these conditions, although in many cases the effect size is small or variable. Caution is recommended when evaluating the genes for which no association was detected, because a number of the investigations reviewed in this article were insufficiently powered to detect small effects. No study has demonstrated a clear-cut altitude illness gene, but the accumulating data are consistent with a polygenic condition with a strong environmental component. The genes that have shown an association affect a variety of biological pathways, suggesting that either multiple systems are involved in altitude pathophysiology or that gene-gene interactions play a role. Although numerous studies have been performed to investigate specific genes, few have looked for evidence of heritability or familial transmission, or for epidemiological patterns that would be consistent with genetically influenced conditions. Future trends, such as genome-wide association studies and epigenetic analysis, should lead to enhanced understanding of the complex interactions within the genome and between the genome and hypoxic environments that contribute to an individuals capacity to acclimatize rapidly and effectively to altitude.

Is Poor Sleep Quality at High Altitude Separate from Acute Mountain Sickness? Factor Structure and Internal Consistency of the Lake Louise Score Questionnaire

BACKGROUND The factor structure and internal consistency of the Lake Louise Score Questionnaire (LLSQ) have not been determined in a large population at high altitude; however, a single-factor structure and a high internal consistency are preferable for accurate clinical and research applications of the LLSQ. METHODS A large group of Nepalese pilgrims (n=491) were assessed for acute mountain sickness with a verbal Nepali translation of the LLSQ after rapidly ascending from 1950 m to 4380 m. The factor structure and internal consistency of the LLSQ were determined with a confirmatory factor analysis (CFA) and the ordinal alpha coefficient, respectively. RESULTS A one-factor structure with all five items of the LLSQ was accepted. Four items (headache, gastrointestinal upset, fatigue/weakness, and dizziness/lightheadedness) loaded strongly on this factor (>0.70), but sleep quality had a low factor loading (0.33). The internal consistency (ordinal alpha coefficient) was 0.79, but removing the sleep quality item improved this value to 0.84. CONCLUSIONS The sleep quality item of the LLSQ was weakly related to the other items of the LLSQ. Future research should further investigate whether impaired sleep at altitude should be considered separately from other symptoms of AMS.

Inhaled salbutamol and doping control: effects of dose on urine concentrations.

Objective:The present study was designed to examine the dose-response relationship of inhaled salbutamol and its concentration in the urine while resting at various times after inhalation, and to compare these values against the current World Anti-Doping Code limits. Design:An interventional, repeated-measures design. Setting:Sport Medicine Clinic, University of British Columbia (Vancouver, Canada). Participants:Eight healthy, nonasthmatic males participated in this study (age = 28 ± 6 years, height = 179.4 ± 5.1 cm, and weight = 77.4 ± 5.4 kg). Intervention:Administration of three different doses of inhaled salbutamol (800, 400, and 200 μg) in a randomized fashion separated by at least 72 hours. Main Outcome Measurement:Urine concentration of nonsulphated salbutamol Results:Urine concentrations were highly variable between subjects and increased as dose increased, with a significant difference noted between 800 and 200 μg at 30, 60, and 120 minutes after inhalation. Urine concentrations of salbutamol peaked at 60 minutes for all doses. No samples exceeded the doping criterion of 1000 ng/mL, and the maximum value observed was 904 ng/mL. Conclusion:These results indicate that after inhalation of doses up to 800 μg, urinary concentrations of salbutamol are well below the limits used in doping control.

Genotype at the Missense G894T Polymorphism (Glu298Asp) in the NOS3 Gene Is Associated with Susceptibility to Acute Mountain Sickness

Acute mountain sickness (AMS) is a potentially serious affliction that frequently occurs in travelers to altitudes above 2500 m. The probability of developing AMS depends on environmental factors such as rate of ascent and altitude attained; however, familial clustering and recurrence rates suggest that there may be a genetic contribution to the etiology of the condition. The underlying pathophysiology of AMS is unknown, but it may involve vasogenic edema secondary to hypoxia-induced sympathetic response and endothelial dysfunction. Nitric oxide is a potent vasomodulator, and variants in the gene that encodes endothelial nitric oxide synthase (NOS3) have been shown to affect blood pressure. We tested the hypothesis that haplotypes, as determined by tagSNPs, in NOS3 would be differentially represented in individuals with and without AMS sampled at the Janai Purnima Festival at Lake Gosain Kunda, Nepal, at 4380 m. Seven SNPs were tested, and a highly significant association (p = 0.004) was found for genotypes of the commonly studied missense polymorphism Glu298Asp (rs 1799983; G/T transversion at base 894). The T allele, which previously has been associated with hypertension, was overrepresented in individuals with AMS (0.30 vs. 0.10), but not significantly when the data were corrected for multiple testing (p = 0.024). These data suggest that a variant in a gene involved in nitric oxide synthesis is a risk factor for developing AMS.

The Genetics of Altitude Tolerance: The Evidence for Inherited Susceptibility to Acute Mountain Sickness

Objective: Acute mountain sickness (AMS) has become a significant environmental health issue as improvements in transportation, “environmental tourism,” and resource development lure more people to the highlands. Whether there is a genetic contribution to AMS susceptibility is a central question in high-altitude medicine. This article provides a systematic review of the evidence supporting such an innate predisposition. Methods: Scientific literature databases were screened using the terms “acute mountain sickness/AMS” and “altitude illness” combined with the terms “DNA,” “gene,” “genetic,” or “polymorphism.” Results: Sixteen genes from a variety of pathways have been tested for association with AMS and variants in eight showed positive associations suggesting that AMS is an environmentally mediated polygenic disorder. Conclusions: The data suggest that genotype contributes to capacity to rapidly and efficiently acclimatize to altitude; nevertheless, the mechanisms by which this occurs have yet to be elucidated.

Evaluation of the Balance Error Scoring System (BESS) in the Diagnosis of Acute Mountain Sickness at 4380 m

Ascent to altitude is associated with a decrease in balance; however, the effect of acute mountain sickness (AMS) status on balance is variable depending on the test used and the altitude at which the test is performed. Here, we report preliminary findings on the relationship between the balance error scoring system (BESS) and AMS at the 2010 Janai Purnima festival at Gosainkunda, Nepal (4380 m). All subjects (n=37) completed a shortened BESS test (mBESS) while a subset completed the full BESS test (n=27). Pulse oximetry was used to measure heart rate and oxygen saturation, and blood pressure was measured by sphygmomanometer. Balance test scores (BESS and mBESS) and physiological measurements were compared between groups with AMS (AMS⁺) and without AMS (AMS⁻). Receiver-operator characteristic (ROC) curves were used to compare the abilities of the BESS and mBESS tests to correctly identify the AMS status of subjects. The AMS⁺ group had significantly higher Lake Louise scores than the AMS⁻ group (mean=4.0 (standard deviation=1.3) vs. 0.3 (0.6), p<0.001). The AMS⁺ group also scored significantly higher on both the mBESS (6.6 (3.5) vs. 2.7 (1.7) errors, p=0.018) and the BESS tests (19.2 (8.8) vs. 10.4 (6.0) errors, p=0.001) compared to the AMS⁻ group, indicating inferior balance in the AMS⁺ group. The area under the ROC curve was significantly greater for the BESS test (0.895) compared to the mBESS test (0.690, p=0.02), implying that the full BESS test more accurately identified a subjects AMS status. Additional studies are needed to determine if BESS could be a useful adjunct to the clinical diagnosis of AMS.